NMO Increases Women's Risk of Miscarriage, Preeclampsia

Autoimmune eye disease may have ripple effects in pregnancy

Action Points

Women diagnosed with aquaporin-4 positive (AQP4) neuromyelitis optica spectrum disorder (NMOSD) had an increased risk of miscarriage and preeclampsia, according to a small retrospective study in the U.K., Portugal, and Japan found.

Note that risk of miscarriage was much greater among women becoming pregnant after rather than before NMOSD onset, but timing of NMOSD onset had minimal impact on the elevated rate of preeclampsia.

Women diagnosed with aquaporin-4 positive (AQP4) neuromyelitis optica spectrum disorder (NMOSD) had an increased risk of miscarriage and preeclampsia, a small retrospective study of women with NMOSD in the U.K., Portugal, and Japan found.

The risk of miscarriage was much greater among women becoming pregnant after NMOSD onset, independent of maternal age. Nearly half of women miscarried when the pregnancy was after the onset of the disorder (43%, 95% CI 18%-71%) compared to 7% of women who were pregnant before NMOSD onset (95% CI 2%-16%), reported Matthew M. Nour, BM, BCh, of the University of Oxford in England, and colleagues.

In fact, women with pregnancies occuring at any point after NMOSD onset had a seven-fold increase in miscarriage risk (odds ratio 7.28, 95% CI 1.03-51.6, P=0.047), with even higher rates of miscarriage occurring within 3 years of NMOSD onset (OR 11.6, 95% CI 1.05-1.28, P=0.046), they wrote in Neurology.

NMOSD is an inflammatory, autoimmune disorder with clinical symptoms affecting vision but that also involves neurodegeneration in the brain and brainstem. Its prevalence has been estimated at 0.5 to 4 per 100,000. The disorder was often conflated with multiple sclerosis (which also has optic neuritis as a common manifestation) until AQP4 was confirmed as the autoimmune target unique to NMO.

Richard Burwick, MD, assistant professor, Department of Obstetrics and Gynecology at Oregon Health & Science University in Portland, who was not involved with the study, said that the baseline rate of preeclampsia was likely higher due to the fact that nearly two-thirds (63.3%) of study participants had co-existing autoimmune disorders, such as systemic lupus erythematosus and antiphospholipid syndrome, which also predisposes women to preeclampsia. He also offered a potential explanation for the high rates of miscarriage.

"It is worth noting that other research has shown that women with AQP4-positive NMOSD have circulating [immunoglobulin or IgG] antibodies that may bind placental AQP4, triggering placental injury," Burwick wrote in an email to MedPage Today. "Due to the uncommon nature of NMOSD, overall interpretations of this study are limited, but all women with NMOSD considering pregnancy should consult a maternal fetal medicine physician."

Nour's team examined 60 AQP4-seropositive women with 126 pregnancies occurring from 1963-2013. The preeclampsia analysis used pregnancies from all 3 centers (n=57), but the Japanese cohort did not include pregnancy information and was excluded from the miscarriage analysis (n=40). Mean age of disease onset was 46.4 years, with isolated ON (42%), transverse myelitis or an inflammation of the spinal cord (38%), or brain involvement (18%). Patients were started on immunotherapy an average of 47.2 months from disease onset and eight pregnancies occurred during the course of treatment.

The baseline rate of preeclampsia was higher in women with NMOSD compared to control populations in other studies, the authors noted (11.5% versus 3.1%, P<0.0001). However, timing of NMOSD onset seemed to have minimal impact on the rate of preeclampsia, with 11.2% (95% CI 5.74%-9.2%) before NMOSD onset and 13.3% (95% CI 1.66%-40.5%) occurring after onset of the disorder.

Not surprisingly, statistically significant increased risks of preeclampsia were associated with miscarriage in the most recent pregnancy (OR 27.2, 95% CI 1.75-4.75, P=0.023) and history of at least two other autoimmune disorders (OR 8.01, 95% CI 1.03-62.6, P=0.047).

In addition, increased disease activity unsurprisingly played a role in the potential for miscarriage. The mean annual relapse rate (ARR) was higher from 9 months preconception to the end of the pregnancy in the miscarriage subgroup compared to the viable pregnancy subgroup (ARR 0.707 versus 0.100, P=0.0152).

There was one infant born with hydrocephalus and permanent neurologic disability, though the mother had preeclampsia, as well as undiagnosed and untreated AQP4-IgG-positive relapsing optic neuritis (inflammation of the optic nerve and one of the main symptoms of NMODS) 4 years prior to conception. There were no stillbirths in the cohort.

Limitations to the study include the small sample size due to the rarity of the disease, its retrospective design, and the lack of pathologic evidence from placenta samples.

Nour and colleagues concluded that further research is needed on NMOSD to ensure patients receive better care, especially during pregnancy.

"Larger prospective studies with age-matched controls are required to extend our findings and to allow better evidence-based treatment approaches before, during and after pregnancy to reduce disease activity, prevent attacks, and avoid complications of both pregnancy and NMOSD," they wrote.

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